1. Field of the Invention
Example embodiments of the present invention relate in general to the field of a pharmaceutical use of poly-gamma-glutamic acid used for preventing or treating Th17-mediated diseases, and more specifically, to a pharmaceutical composition for preventing or treating Th17-mediated diseases including poly-gamma-glutamic acid as an active ingredient.
2. Description of the Related Art
A human body in general raises a defensive immune response against foreign substances, but is not reactive against substances in his or her own body. The above phenomenon in which the human body is not immune against substances in his or her own body is known as ‘immunological self-tolerance.’ In order to maintain this phenomenon, the body operates two different mechanisms: (1) a ‘clonal deletion’ mechanism by central immune organs to eliminate T cells which are reactive to autoantigens and (2) a ‘regulation’ mechanism by peripheral immune organs to suppress the activities of T cells which are reactive to autoantigens. Failure of the immunological self-tolerance causes autoimmune diseases.
Regulatory T (Treg) cells are major suppressor cells that mediate the above ‘regulation’ mechanism. The Treg cells were originally known as a minor population of cells generated in the thymus via an intrinsic pathway and distributed in the periphery, but they are now known to be generated in the periphery as well. That is, naïve CD4+ T cells, which are present in the periphery rather than the thymus, can express Foxp3 in response to antigenic stimulation in the presence of TGF-β, and differentiate into Treg cells. These Treg cells play a crucial role in the mechanism of ‘immunological self-tolerance.’
In contrast, Th17 cells are representative proinflammatory cells. Th17 cells, being a different subset from Th1 and Th2 cells, secrete IL-17, IL-17F, IL-21, and IL-22. Naïve CD4+ T cells can be differentiated into Th17 cells in vitro in response to antigenic stimulation in the presence of TGF-β and IL-6, and transcription factors such as RORγt, STAT-3, and IRF4 are involved in this process. Th17 cells infiltrated into the peripheral tissues act on macrophages, dendritic cells, fibroblasts, vascular endothelial cells, osteoclasts, etc., and secrete various inflammatory cytokines (IL-1, TNF, IL-8, IL-6, etc.), chemokines, MMPs, etc., thereby causing tissue damage. These Th17 cells are major pathologic cells that mediate inflammatory diseases.
As described above, Treg cells and Th17 cells are contrary to each other in their roles, but their generations in the periphery share the common precursor cells and are interrelated. That is, when CD4 positive T cells are differentiated by TGF-β and antigenic stimulation, whether they are differentiated into Treg cells or Th17 cells is determined based on the presence of other inflammatory cytokines such as IL-6, IL-23, IL-1, and IL-21. Therefore, in Th17-mediated diseases which are caused by the imbalance in Th17/Treg or the over-differentiation of Th17 cells, any substance which can suppress the generation of Th17 cells while inducing the generation of Treg cells may be able to remedy the above imbalance and restore immune-homeostasis, thereby being useful for preventing and treating such diseases.
Recently, intensive research has been conducted for the development of a therapeutic agent which can suppress the generation of Th17 cells. As a result, various therapeutic agents, for example, SR1001, which inhibits RORγt, a transcription factor of Th17 cells, Halofuginone, which inhibits only Th17 activity, and anti-IL-17 monoclonal antibody, etc., have been developed. However, these substances have disadvantages in that a great deal of time will be required before they become applicable to patients after undergoing clinical trials, and also in the case of antibodies, the cost to prepare monoclonal antibodies may be prohibitively expensive. Therefore, there is an urgent need for the development of a novel therapeutic agent which is reasonable in cost and is easily applicable to humans while having an excellent therapeutic effect in preventing or treating Th17-mediated diseases.